The aims of the Neuropathology Core are to provide technical resources, laboratory facilities and professional expertise for the collection, diagnosis and storage of brain tissue obtained at autopsy from patients and control subjects studies in the Clinical Core of the Indiana ADC, as well as from referral cases from other institutions. The Neuropathology Core will provide information about pathologic data to families, referring physicians and basic researchers. In addition, the Core will be involved in continuing education to the community about new developments emerging from Alzheimer disease (AD) research. Our understanding of the molecular, biochemical, histochemical, pathologic and clinical aspects of AD has advanced rapidly during the last five years. Thus, brain tissue of demented individuals must be studied for diagnostic and research purposes using a multidisciplinary approach. We have established a Dementia Laboratory, developed a laboratory for morphometric studies of degenerative brain diseases and expanded our Brain Bank. The Core has contributed to the investigations of hereditary presenile dementias with neurofibrillary tangles by (i) characterizing familial AD with a mutation in APP gene, (ii) characterizing the neuropathologic phenotype of Gerstmann-Straussler- Sckeinker (GSS) disease in the Indiana kindred, (iii) studying tau pathology in neurodegenerative disease, (iv) expanding our knowledge on the Neuropathology of diseases caused by mutations in the APP and PRNP genes, (v) discovering new forms of presenile dementias. We are expanding our mission integrating modern molecular technology to assist in the diagnosis of dementias, in particular the cerebral amyloidoses. In fact, we are combining data obtained by neuromorphology, immunohistochemistry, and immunocytochemistry to recognize and characterize the localization and the antigenic profile of molecules that are important to the pathogenesis of dementia of the adult. This analysis is fundamental to explore phenotypic heterogeneity. Furthermore, by using brain tissue obtained at autopsy as well as from paraffin embedded material, we will define the molecular genetics of individual cases. Specifically, we will use technology that allows us to recognize mutations described in genes currently known to cause AD and other dementias. We consider that this multidisciplinary approach required for an ADC Neuropathology Core to provide diagnosis at the histological, biochemical and DNA level, taking full advantage of the collected material.